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Title: IDENTIFICATION OF GENE NETWORKS UNDERLYING MAMMARY TUMOR PROTECTION BY DIETARY EXPOSURE TO SOY AND GENISTEIN

Author
item SU, YING - ACNC/UAMS
item XIAO, RIJIN - ACNC/UAMS
item GENG, YAN - ACNC/UAMS
item SKINNER, CHARLES - ACNC
item SIMMEN, FRANK - ACNC/UAMS
item SIMMEN, ROSALIE - ACNC/UAMS

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 2/6/2006
Publication Date: 3/27/2006
Citation: Su, Y., Xiao, R., Geng, Y., Skinner, C.M., Simmen, F.A., Simmen, R.C. 2006. Identification of gene networks underlying mammary tumor protection by dietary exposure to soy and genistein [abstract]. The FASEB Journal. 20(4):A560.

Interpretive Summary: Soy proteins in the diet can reduce occurrence of breast cancers in rats. One constituent of soy protein is the chemical called genistein, which may be the causative agent for anti-breast cancer effects of diets containing soy. This study examined whether the feeding of genistein would mimic the effects of feeding soy protein in the rat breast cancer model. In addition, we pursued novel gene identification to understand how soy and genistein might be working to suppress breast cancers. This study showed that feeding of genistein did not wholly mimic effects of feeding soy and that they are not one in the same with respect to anti-cancer effects. Secondly, we identified novel genes and gene networks that may be affected by soy and genistein to reduce breast cancer incidence. This study has pointed to new directions that can be followed to further understand the role of diet and cancer risk in humans.

Technical Abstract: We have previously shown that lifetime consumption of soy protein isolate (SPI) reduced the incidence of chemically-induced mammary tumors in young adult rats, relative to those fed the control diet containing Casein (CAS). Genistein (GEN) is a biologically active component of soy foods and is associated with reduced breast cancer risk in women who consume soy-rich diets. To obtain insights into the molecular mechanisms underlying tumor protection by these dietary components, global gene expression profiles of mammary epithelial cells (MEC) isolated from postnatal day 50 rats fed AIN-93G diets with CAS ± GEN or SPI were determined using Affymetrix RAE230A microarrays representing 14,280 genes. We identified 18 induced and 34 repressed genes in the SPI-fed group, and 36 induced and 53 repressed genes in the GEN-fed group, relative to CAS (>1.5-fold difference, P<0.05). MEC from GEN-fed rats had 43 higher and 31 lower expressed genes, than those of SPI-fed rats. The expression patterns of: a) Egr3, quiescin 6, Transferrin Receptor, cadherin 22, estrogen receptor-', PTEN (SPI=GEN >CAS); b) sFRP2, WAP (GEN>SPI=CAS); and c) progesterone receptor (SPI>CAS=GEN) genes were validated using real-time quantitative RT-PCR. Results demonstrate marked GEN effects on gene expression that are not mimicked by SPI. The identification of transcripts co- or differentially-regulated by SPI and GEN suggests common and unique signaling pathways underlying nutritional prevention of mammary tumorigenesis.